Document Detail


Inhibition of the Prohormone Convertase Subtilisin-Kexin Isoenzyme-1 Induces Apoptosis in Human Melanoma Cells.
MedLine Citation:
PMID:  23884247     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Prohormone convertases (PCs) are endoproteases that process many substrates in addition to hormone precursors. Although overexpression of PCs is linked to carcinogenesis in some solid tumors, the role of subtilisin-kexin isoenzyme-1 (SKI-1) in this context is unknown. We show that SKI-1 is constitutively expressed in human pigment cells with higher SKI activity in seven out of eight melanoma cell lines compared with normal melanocytes. SKI-1 immunoreactivity is also detectable in tumor cells of melanoma metastases. Moreover, tissue samples of the latter display higher SKI-1 mRNA levels and activity than normal skin. From various stimuli tested, 12-O-tetradecanoylphorbol-13-acetate and tunicamycin affected SKI-1 expression. Importantly, SKI-1 inhibition by the cell-permeable enzyme inhibitor decanoyl-RRLL-chloromethylketone (dec-RRLL-CMK) not only suppressed proliferation and metabolic activity of melanoma cells in vitro but also reduced tumor growth of melanoma cells injected intracutaneously into immunodeficient mice. Mechanistic studies revealed that dec-RRLL-CMK induces classical apoptosis of melanoma cells in vitro and affects expression of several SKI-1 target genes including activating transcription factor 6 (ATF6). However, ATF6 gene silencing does not result in apoptosis of melanoma cells, suggesting that dec-RRLL-CMK induces cell death in an ATF6-independent manner. Our findings encourage further studies on SKI-1 as a potential target for melanoma therapy.Journal of Investigative Dermatology advance online publication, 25 July 2013; doi:10.1038/jid.2013.282.
Authors:
Nina Weiß; Agatha Stegemann; Marwa A T Elsayed; Karin U Schallreuter; Thomas A Luger; Karin Loser; Dieter Metze; Carsten Weishaupt; Markus Böhm
Related Documents :
24790027 - Toll-like receptor 2 activation by β2->1-fructans protects barrier function of t84 huma...
23166357 - Rae-1 ligands for the nkg2d receptor are regulated by e2f transcription factors, which ...
23155237 - Cytotoxicity and type of cell death induced by midazolam in human oral normal and tumor...
22975317 - Orienting the direction of egfr activation.
10924267 - Green fluorescent protein: a novel viability assay for cryobiological applications.
3588837 - Repair and fixation of potentially lethal damage (pld) as demonstrated by delayed plati...
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-6-27
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  -     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-7-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Laboratory for Neuroendocrinology of the Skin and Interdisciplinary Endocrinology, Department of Dermatology, University of Münster, Münster, Germany.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Plakophilin 2 affects cell migration by modulating focal adhesion dynamics and integrin protein expr...
Next Document:  Impact of aspirin dose on adenosine diphosphate-mediated platelet activity. Results of an in vitro p...